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Tài liệu Báo cáo khoa học: Switching of the homooligomeric ATP-binding cassette transport complex
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Mô tả chi tiết
Switching of the homooligomeric ATP-binding cassette
transport complex MDL1 from post-translational
mitochondrial import to endoplasmic reticulum insertion
Simone Gompf1
, Ariane Zutz1
, Matthias Hofacker1
, Winfried Haase2
, Chris van der Does1
and Robert Tampe´
1
1 Institute of Biochemistry, Biocenter, Johann Wolfgang Goethe-University, Frankfurt am Main, Germany
2 Max-Planck Institute of Biophysics, Structural Biology, Frankfurt am Main, Germany
ATP-binding cassette (ABC) transporters belong to a
large family of membrane proteins found in all three
kingdoms of life. The chemical energy of ATP is used
to drive uphill transport of a broad range of solutes
across membranes [1–3]. ABC transporters have a
conserved domain organization consisting of two transmembrane domains (TMDs) and two nucleotide-binding domains (NBDs). The TMDs form a translocation
pore, whereas the NBDs catalyze ATP hydrolysis.
The ABC half-transporter multidrug resistance like
protein 1 (MDL1), composed of a TMD followed by a
NBD, is located in the inner mitochondrial membrane
(IMM) of Saccharomyces cerevisiae. It has been suggested to be involved in the export of 6-mer to 20-mer
peptides, derived from proteolysis of nonassembled
inner membrane proteins by the m-AAA (i.e. matrixoriented ATPase associated with a variety of cellular
activities) protease [4]. It has been further reported
that MDL1 mediates resistance against oxidative stress
and can partially complement the function of ABC
transporter of mitochondria (ATM) 1 [5]. Deletion of
ATM1 in S. cerevisiae results in a severe growth defect
because ATM1 is essential for the biogenesis of cytosolic iron-sulfur (Fe-S) proteins [6].
Keywords
ABC transporter; ER targeting; membrane
protein trafficking transport ATPase;
mitochondrial import; mitochondrial
targeting sequence
Correspondence
R. Tampe´, Institute of Biochemistry,
Biocenter, Johann Wolfgang GoetheUniversity, Max-von-Laue-Strasse 9,
D-60348 Frankfurt am Main, Germany
Fax: +49 (0) 69 798 29495
Tel: +49 (0) 69 798 29475
E-mail: tampe@em.uni-frankfurt.de
Website: http://www.biochem.
uni-frankfurt.de
(Received 25 May 2007, revised 5 July
2007, accepted 20 August 2007)
doi:10.1111/j.1742-4658.2007.06052.x
The ATP-binding cassette transporter MDL1 of Saccharomyces cerevisiae
has been implicated in mitochondrial quality control, exporting degradation
products of misassembled respiratory chain complexes. In the present study,
we identified an unusually long leader sequence of 59 amino acids, which
targets MDL1 to the inner mitochondrial membrane with its nucleotidebinding domain oriented to the matrix. By contrast, MDL1 lacking this leader sequence is directed into the endoplasmic reticulum membrane with the
nucleotide-binding domain facing the cytosol. Remarkably, in both targeting routes, the ATP-binding cassette transporter maintains its intrinsic
properties of membrane insertion and assembly, leading to homooligomeric
complexes with similar activities in ATP hydrolysis. The physiological consequences of both targeting routes were elucidated in cells lacking the mitochondrial ATP-binding cassette transporter ATM1, which is essential for
biogenesis of cytosolic iron-sulfur proteins. The mitochondrial MDL1 complex can complement ATM1 function, whereas the endoplasmic reticulumtargeted version, as well as MDL1 mutants deficient in ATP binding and
hydrolysis, cannot overcome the Datm1 growth phenotype.
Abbreviations
ABC, ATP-binding cassette; ATM, ABC transporter of mitochondria; ER, endoplasmic reticulum; 5-FOA, 5-fluoroorotic acid; IMM, inner
mitochondrial membrane; MDL1, multidrug resistance like protein 1; MTS, mitochondrial targeting signal; NBD, nucleotide-binding domain;
SC, synthetic complete; TIM, translocase of the inner mitochondrial membrane; TOM, translocase of the outer mitochondrial membrane;
TMD, transmembrane domain.
5298 FEBS Journal 274 (2007) 5298–5310 ª 2007 The Authors Journal compilation ª 2007 FEBS